Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that data from HAVEN 1, a phase III study evaluating once-weekly subcutaneous emicizumab prophylaxis (preventative) in adults and adolescents with haemophilia A with inhibitors, were published in The New England Journal of Medicine (NEJM). The primary endpoint showed a clinically meaningful and statistically significant reduction in treated bleeds of 87% (risk rate [RR]=0.13, p<0.0001) with emicizumab prophylaxis compared with on-demand (no prophylaxis; episodic use only) bypassing agents (BPAs). All 12 secondary endpoints were positive, including a statistically significant reduction of 79% (RR=0.21, p=0.0003) in treated bleeds in a first of its kind intra-patient analysis in a subset of patients comparing two prophylaxis regimens (emicizumab and BPAs). Data from HAVEN 1 as well as the interim analysis of the phase III HAVEN 2 study of emicizumab in children are being presented at the 26th International Society on Thrombosis and Haemostasis (ISTH) Congress today.
"Nearly one in three people with haemophilia A develop inhibitors to standard factor VIII therapy, leaving them at greater risk of life-threatening bleeds and long-term joint damage," said Sandra Horning, MD, Roche's Chief Medical Officer and Head of Global Product Development. "Based on the bleed reduction shown in the HAVEN 1 and HAVEN 2 studies, we believe emicizumab has the potential to make a meaningful difference for people with haemophilia A with inhibitors, while also reducing the burden of managing the condition with a subcutaneous, once-weekly administration."
Further data from HAVEN 1 showed that, after a median observation time of 31 weeks, substantially more patients experienced zero bleeds with emicizumab prophylaxis than with on-demand BPAs across all bleed measurements, including zero treated bleeds (62.9% vs 5.6%), zero treated spontaneous bleeds (68.6% vs 11.1%), zero treated joint bleeds (85.7% vs 50.0%), zero treated target joint bleeds (94.3% vs 50.0%) and zero bleeds overall, which includes all treated and non-treated bleeds (37.1% vs 5.6%). A clinically meaningful and statistically significant improvement in health-related quality of life (HRQoL) measured at 25 weeks, using two validated instruments (Haem-A-QoL and EQ-5D-5L), was also observed.
In an additional study arm (Arm C, n=49), patients who had previously received BPA prophylaxis were treated with emicizumab prophylaxis. A subset of patients in this arm (n=24) had previously participated in a non-interventional study (NIS), allowing for a first of its kind intra-patient analysis comparing two prophylaxis regimens. This analysis showed a 79% (RR=0.21, p=0.0003) reduction in treated bleeds in patients receiving emicizumab compared with their prior BPA prophylaxis during the NIS. Data also showed that 70.8% of patients in this subset experienced zero treated bleeds with emicizumab prophylaxis whereas only 12.5% of these patients had experienced zero bleeds with their prior BPA prophylaxis during the NIS.
"The HAVEN 1 study is one of the most robust clinical studies conducted to date in people with haemophilia A with inhibitors to factor VIII, including a first ever intra-patient comparison to prior prophylaxis with bypassing agents," said Professor Johannes Oldenburg, Institute of Experimental Haematology and Transfusion Medicine, University of Bonn, Germany. "The reduction in bleeding events across all measures seen with emicizumab compared to either on-demand or prophylactic bypassing agents supports that it may be one of the most significant scientific innovations in the treatment of haemophilia A in over 30 years."
Adverse events (AEs) occurring in 5% or more of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection and joint pain (arthralgia). As previously reported, serious adverse events of thromboembolic events (TE) and thrombotic microangiopathy (TMA) occurred in two patients and three patients*, respectively, while receiving emicizumab prophylaxis. The common aspect of these TMA** and TE events is the patients were on emicizumab prophylaxis and received more than 100 u/kg/day of the BPA activated prothrombin complex on average for 24 hours or more before the onset of the event. Neither TE event required anti-coagulation therapy and one patient restarted e...
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